title: NSAID-induced gastrointestinal damage and the design of GI-sparing NSAIDs.
abstract: NSAIDs are among the most widely used medications, but the side effects of these drugs frequently include gastrointestinal (GI) ulceration and bleeding. COX-2 inhibitors were designed that were claimed to be devoid of ulcer-promoting effects; however, this promise has been unfulfilled, and there are concerns about the cardiovascular safety of COX-2 inhibitors. Several novel approaches to developing GI-sparing NSAIDs have been used, with promising preclinical and clinical results. Selective inhibition of terminal PG synthases, and NSAIDs modified to slowly release gastroprotective gaseous mediators (ie, nitric oxide or hydrogen sulfide) may offer renewed hope for developing anti-inflammatory therapies with greatly reduced GI toxicity.
authors.affiliation: University of Calgary, Department of Pharmacology & Therapeutics, Calgary, Alberta T2N 4N1, Canada. wallacej@ucalgary.ca
authors.forename: John L
authors.initials: JL
authors.lastname: Wallace
authors.forename: Linda
authors.initials: L
authors.lastname: Vong
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects; D015195:Drug Design; D041981:Gastrointestinal Tract / Q000187:drug effects*; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D011448:Prostaglandin Antagonists / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011448:Prostaglandin Antagonists; D009569:Nitric Oxide; D006862:Hydrogen Sulfide